Clinical Translation of Tissue Engineered Trachea Grafts

Chiang, Tendy; Pepper, Victoria K.; Best, Cameron; Onwuka, Ekene; Breuer, Christopher K.

doi:10.1177/0003489416656646

Cited by 81 publications

(77 citation statements)

References 78 publications

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“…Tracheal tissue engineering, which incorporates cells into a biodegradable scaffold, has emerged as a promising alternative for those patients who lack an appropriate tracheal substitute. [19] Decellularized tracheal matrices have attracted much attention in recent years because of their similar composition and microenvironments to natural tracheal cartilage. [7a] However, the dense tracheal cartilage matrix makes it difficult for original cellular materials to be detached from or for new cells to grow into the matrix.…”

Section: Discussionmentioning

confidence: 99%

Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

Duan

et al. 2020

Adv Funct Materials

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Wharton's jelly (WJ) is considered a potential scaffold in tissue‐engineered trachea for its similar composition and function to cartilage tissue. However, the feasibility of using WJ to construct engineered neocartilage tissue has not been reported, let alone tubular tracheal cartilage regeneration and segmental tracheal lesion repair. Here, electrospun nanofibrous membranes composed of three different decellularized WJ matrix (DWJM)/poly(ε‐caprolactone) (PCL) ratios (8:2, 5:5, and 2:8) are fabricated. The results demonstrate improved degradation speed, absorption, and cell adhesion capacity but weakened mechanical properties with increased DWJM content, but satisfactory homogeneous cartilage regeneration is only achieved in the DWJM/PCL (8:2) group after 12 weeks in vivo culture. Furthermore, homogeneous, 3D, tubular, trachea‐shaped cartilage is constructed with a controllable lumen diameter and wall thickness based on the 2D nanofibrous membrane using a modified sandwich model, in which the chondrocyte‐membrane construct is rolled around a silicon tube. Most importantly, by combining the above schemes with previously established vascularization and epithelialization techniques, chondrification, vascularization, and epithelialization are achieved simultaneously thus realizing long‐term (6 months) circumferential tracheal lesion repair in a rabbit model with a biological structure and function similar to that of native trachea, representing a promising approach for the clinical application of tracheal tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

Duan

et al. 2020

Adv Funct Materials

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“…This is partly because implant sites typically experience air flow, neck movement, and bacterial infection during the remodeling process. Thus, clinical trials of artificial trachea have been largely unsuccessful 27,28 . New strategies for tracheal regeneration are therefore required.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes

Kim

Park

Lee

et al. 2020

Sci Rep

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For successful tracheal reconstruction, tissue-engineered artificial trachea should meet several requirements, such as biocompatible constructs comparable to natural trachea, coverage with ciliated respiratory mucosa, and adequate cartilage remodeling to support a cylindrical structure. Here, we designed an artificial trachea with mechanical properties similar to the native trachea that can enhance the regeneration of tracheal mucosa and cartilage through the optimal combination of a two-layered tubular scaffold and human induced pluripotent stem cell (iPSC)-derived cells. The framework of the artificial trachea was fabricated with electrospun polycaprolactone (PCL) nanofibers (inner) and 3D-printed PCL microfibers (outer). Also, human bronchial epithelial cells (hBECs), iPSCderived mesenchymal stem cells (iPSC-MSCs), and iPSC-derived chondrocytes (iPSC-Chds) were used to maximize the regeneration of tracheal mucosa and cartilage in vivo. After 2 days of cultivation using a bioreactor system, tissue-engineered artificial tracheas were transplanted into a segmental trachea defect (1.5-cm length) rabbit model. Endoscopy did not reveal granulation ingrowth into tracheal lumen. Alcian blue staining clearly showed the formation of ciliated columnar epithelium in iPSC-MSC groups. In addition, micro-CT analysis showed that iPSC-Chd groups were effective in forming neocartilage at defect sites. Therefore, this study describes a promising approach for long-term functional reconstruction of a segmental tracheal defect.

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“…Attempts at airway replacement with artificial material, autologous tissue transplant, or cadaveric transplantation have been limited by chronic infection, graft collapse, vascular erosion, or the need for life-long immunosuppression [2,3]. Tissue engineering offers an alternative that may mitigate many of these concerns.…”

Section: Introductionmentioning

confidence: 99%

“…Isolated case reports describing the compassionate use of tissue-engineered tracheal grafts have used a variety of techniques and materials including decellularized cadaveric grafts and biosynthetic materials. In each case, significant complications have occurred requiring multiple hospitalizations and additional procedures [3–6]. …”

Section: Introductionmentioning

confidence: 99%

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Designing a tissue-engineered tracheal scaffold for preclinical evaluation

Best

Pepper

Ohst

et al. 2018

International Journal of Pediatric Otorhinolaryngology

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Objective Recent efforts to tissue engineer long-segment tracheal grafts have been complicated by stenosis and malacia. It has been proposed that both the mechanical characteristics and cell seeding capacity of TETG scaffolds are integral to graft performance. Our aim was to design a tracheal construct that approximates the biomechanical properties of native sheep trachea and optimizes seeding with bone marrow derived mononuclear cells prior to preclinical evaluation in an ovine model. Methods A solution of 8% polyethylene terephthalate (PET) and 3% polyurethane (PU) was prepared at a ratio of either 8:2 or 2:8 and electrospun onto a custom stainless steel mandrel designed to match the dimensional measurements of the juvenile sheep trachea. 3D-printed porous or solid polycarbonate C-shaped rings were embedded within the scaffolds during electrospinning. The scaffolds underwent compression testing in the anterior-posterior and lateral-medial axes and the biomechanical profiles compared to that of a juvenile ovine trachea. The most biomimetic constructs then underwent vacuum seeding with ovine bone marrow derived mononuclear cells. Fluorometric DNA assay was used to quantify scaffold seeding. Results Both porous and solid rings approximated the biomechanics of the native ovine trachea, but the porous rings were most biomimetic. The load-displacement curve of scaffolds fabricated from a ratio of 2:8 PET:PU most closely mimicked that of native trachea in the anterior-posterior and medial-lateral axes. Solid C-ringed scaffolds had a greater cell seeding efficiency when compared to porous ringed scaffolds (Solid: 19 × 104 vs. Porous: 9.6 × 104 cells/mm3, p = 0.0098). Conclusion A long segment tracheal graft composed of 2:8 PET:PU with solid C-rings approximates the biomechanics of the native ovine trachea and demonstrates superior cell seeding capacity of the two prototypes tested. Further preclinical studies using this graft design in vivo would inform the rational design of an optimal TETG scaffold.

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Clinical Translation of Tissue Engineered Trachea Grafts

Cited by 81 publications

References 78 publications

Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes

Designing a tissue-engineered tracheal scaffold for preclinical evaluation

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